Glaucoma is a disease of the eye characterized by elevated intraocular pressure. The elevated intraocular pressure leads to hardening of the eyeball, narrowing of the field of vision and a decrease in a subject""s visual acuity. Glaucoma is a disease of the optic nerve and the elevated eye pressures are related to damage of this nerve. The optic nerve carries images from the retina to the brain. Glaucoma damages optical nerve cells causing blindspots to occur within a subject""s vision. These blind spots typically are not noticed by the subject until considerable damage to the optic nerve has already occurred. The terminal stage of glaucoma is total blindness of the subject.
Approaches to treating glaucoma include the topical application of cholinergic agents, e.g., pilocarpine, alpha- or beta- adrenergic agonists or antagonists, e.g., clonidine, timolol or epinephrine. An alternative approach for treating glaucoma is the systemic administration of carbonic anhydrase inhibitors. In some cases laser or operative surgery is used to treat glaucoma.
Problems exist with the aforementioned approaches to treating glaucoma in that the treatments can be accompanied by side-effects. For example the instillation of a cholinergic agent, such as pilocarpine, into the eye of a subject can cause nausea, diarrhea, muscular spasms, sweating, lacrimation, salivation, etc. Contraction of the pupil (myosis) and of the ciliary muscle of the eye, as well as dilation of the blood vessels of the iris and conjunctiva also can be observed. Visual complications, e.g., spasm of accommodation, myopia or a decrease in visual acuity, also can occur.
The treatment with a sympathomimetic agent such as dipivalylepinephrine is known frequently to produce sensations of burning or irritation in a subject. Another side-effect of these agents is the appearance of cardiac disturbances, e.g., palpitations, tachycardia, arrythmia, etc.
Clonidine, which is known as an alpha-2-adrenergic receptor agonist, can bring about mydriasis, as well as an initial phase of ocular hypertension (biphasic effect). Furthermore, in spite of the topical application of the product to the eye, important systemic effects, such as bradycardia and hypotension, have been observed.
The use of beta-blocking medicaments also can cause important systemic effects after topical administration to the eye, due to the absence of a xe2x80x9cfirst pass effectxe2x80x9d. Timolol, for example, causes bradycardia or hypotension. These systemic secondary reactions to beta-blocking medicaments can reach such a severe level that the treatment has to be discontinued. Cases of suicidal depression, hallucinations, nightmares or psychoses requiring hospitalization have been reported in connection with these medicaments. Furthermore, these compounds have to be administered with extreme precautions to patients subject to cardiac or pulmonary functional disorders. In such patients, amongst others, cases of arrhythmia, cardiac arrest, asthma, dyspnea and bronchospasms have been reported.
The treatment with a sympatholytic agent, such as guanethidine, causes hyperemia of the conjunctiva and some irritation, not to mention the fact that these agents only have a low tendency to reduce intraocular pressure.
Finally, in the treatment of glaucoma with carbonic anhydrase inhibitors, such as acetazolamide or methazolamide, serious systemic side-effects, such as depression of the central nervous system, weight loss and, mainly, bone marrow hypofunction, have been reported.
The use of conventional hypotensive agents for the treatment of glaucoma is accompanied by considerable risks. Known medications are not particularly well suited for topical treatment and the systemic side-effects of these medicaments make them delicate to use because these effects are far from being negligible and because they can have, in some cases, severe consequences.
This invention provides methods and kits useful for the treatment of glaucoma. In one aspect, the methods of the invention include administering a therapeutically effective amount of a deprenyl compound to a subject such that the subject is treated for glaucoma. In a preferred embodiment, the deprenyl compound is represented by the structure: 
in which R1 is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl; R2 is hydrogen or alkyl; R3 is a single bond, alkylene, or xe2x80x94(CH2)nxe2x80x94Xxe2x80x94(CH2)m in which X is O, S, or N-methyl; m is 1 or 2, and n is 0,1, or 2; R4 is alkyl, alkenyl, alkynyl, heterocyclyl, aryl or aralkyl; R5 is alkylene, alkenylene, alkynylene and alkoxylene; and R6 is C3-C6 cycloalkyl or
xe2x80x94Cxe2x89xa1CH; or
R2 and R4-R3 are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group; and pharmaceutically acceptable salts thereof. In preferred embodiments, R1 is a group that can be removed in vivo; R1 is hydrogen; R1 is alkyl; R1 is methyl; R2 is methyl; R3 is methylene; R4 is aryl; or R4 is phenyl. In still other preferred embodiments, R5 is alkylene, more preferably methylene. In other preferred embodiments, R6 is xe2x80x94Cxe2x89xa1CH. In other preferred embodiments, R6 is cyclopentyl.
In another embodiment, the deprenyl compound has the structure 
in which R1 is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl.
In another preferred embodiment, the deprenyl compound is represented by the structure: 
in which R1 is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl; R2 is hydrogen or alkyl; R3 is a bond or methylene; and R4 is aryl or aralkyl; or R2 and R4-R3 are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group; and pharmaceutically acceptable salts thereof.
In another embodiment, the deprenyl compound is represented by the structure: 
in which
R2 is hydrogen or alkyl; R3 is a bond or methylene; and R4 is aryl or aralkyl; or R2 and R4-R3 are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group; and R5 is alkylene, alkenylene, alkynylene and alkoxylene; and pharmaceutically acceptable salts thereof.
In yet another embodiment, the deprenyl compound is represented by the structure: 
in which R1 is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl; A is a substituent independently selected for each occurence from the group consisting of halogen, hydroxyl, alkyl, alkoxyl, cyano, nitro, amino, carboxyl, xe2x80x94CF3, or azido; n is 0 or an integer from 1 to 5; and pharmaceutically acceptable salts thereof.
In other preferred embodiments, the deprenyl compound is (xe2x88x92)-deprenyl, (xe2x88x92)-pargyline, or (xe2x88x92)-desmethyldeprenyl.
In another aspect, the invention provides a kit useful for the treatment of glaucoma. In one embodiment, the kit includes a container of a deprenyl compound and instructions for administering a therapeutically effective amount of the deprenyl compound to a subject such that the subject is treated for glaucoma.